Chen Qianwen, Zhang Wenjuan, Xie Tian, Dong Jiangtao, Zhang Junxia, Zha Lingfeng
Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Med Sci. 2025 Apr 13;22(9):2155-2164. doi: 10.7150/ijms.102562. eCollection 2025.
Coronary artery disease (CAD) involves inflammation. IL-12p35, a common subunit of both IL-12 and IL-35, is encoded by the gene and is a potential therapeutic target in CAD. We probed into the genetic relationships between and CAD in a Chinese Han population to provide a novel potential target and a theoretical basis for the anti-inflammatory therapies in CAD. In total, 768 patients with CADs and 768 controls were recruited for a case-control association analysis of the functional genetic variant rs2243115 of . Allelic and genotypic associations between rs2243115 and CAD and its subgroup were assessed by Logistic regression analysis. Additionally, multiple linear regression analysis was performed to explore the association between rs2243115, serum lipid levels and CAD severity. Bioinformatic tools were used to predict the potential function of rs2243115. Our results showed no differences in the allele and genotype frequency distribution of rs2243115 between patients with CAD and controls. The subgroup analysis found no association between rs2243115 and CAD in either male or female groups. Furthermore, rs2243115 was not related to early- or late-onset CAD, or CAD severity. However, we did observe that rs2243115 was negatively related to HDL-c level (=0.016, 0.063) and positively related to LDL-c level (=0.029, =0.058). Biological function prediction indicated many functional elements in the rs2243115 region, suggesting that rs2243115 may regulate gene expression in the IL-12/IL-35 pathway. The functional genetic variant, rs2243115, of , may play a role in CAD by regulating the IL-12/IL-35 pathway and affecting lipid levels and inflammatory responses, thereby providing a potential therapeutic target for CAD.
冠状动脉疾病（CAD）涉及炎症。IL-12p35是IL-12和IL-35的共同亚基，由该基因编码，是CAD的一个潜在治疗靶点。我们在中国汉族人群中探究了该基因与CAD之间的遗传关系，为CAD的抗炎治疗提供新的潜在靶点和理论依据。总共招募了768例CAD患者和768例对照，对该基因的功能遗传变异rs2243115进行病例对照关联分析。通过逻辑回归分析评估rs2243115与CAD及其亚组之间的等位基因和基因型关联。此外，进行多元线性回归分析以探究rs2243115、血脂水平与CAD严重程度之间的关联。使用生物信息学工具预测rs2243115的潜在功能。我们的结果显示，CAD患者与对照之间rs2243115的等位基因和基因型频率分布没有差异。亚组分析发现，rs2243115在男性或女性组中与CAD均无关联。此外，rs2243115与早发或晚发CAD或CAD严重程度无关。然而，我们确实观察到rs2243115与高密度脂蛋白胆固醇（HDL-c）水平呈负相关（P = 0.016，β = -0.063），与低密度脂蛋白胆固醇（LDL-c）水平呈正相关（P = 0.029，β = 0.058）。生物学功能预测表明rs2243115区域存在许多功能元件，提示rs2243115可能调节IL-12/IL-35途径中的基因表达。该基因的功能遗传变异rs2243115可能通过调节IL-12/IL-35途径并影响血脂水平和炎症反应在CAD中发挥作用，从而为CAD提供一个潜在的治疗靶点。
